In the circulation, human plasma lipoproteins transport lipids which are solubilized by apolipoproteins. The apolipoproteins also function in lipid metabolism. To better understand this structure/function relationship it is necessary to obtain basic information about the physical properties of the apolipoproteins. This proposal deals with the solution properties of the major apolipoproteins; their thermodynamic stability, mechanisms of folding (kinetics), and hydrophobic ligand binding reactions. These same thermodynamic and kinetic processes will also be studied in small synthetic peptides, which mimick apoliprotein structure and function. In studies with synthetic peptides, particular attention will be paid to the role of the putative amphipathic helix in modulating physical properties. Fluorescence and circular dichroic spectroscopic methods will be used to assess apolipoprotein structrual stability and flexibility. Another facet of these experiments involves thermodynamic studies under high pressures. Rapid kinetic techniques (stopped-flow and temperature jump) will measure the rates of apolipoprotein (peptide) conformational change. In the kinetic experiments, mechanisms for folding reactions unique to apolipoproteins are sought. Stopped-flow experiments will measure the kinetics of ligand binding to apolipoproteins, the extent of which will be established by equilibrium dialysis and fluorescence titration. These proposed studies should enhance our understanding of plasma lipoproteins and their role in atherosclerosis.